Methyl iodide → HCID 69056920, compound

HRID 2100580Notes

Reaction equation

HRID 2100580 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:13]2[C:12]([C:14]([F:17])([F:16])[F:15])=[CH:11][CH:10]=[CH:9][C:8]=2[C@@H:7]2[CH2:18][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:20][C@H:6]2[NH:5]1.I[CH3:29]>C1COCC1>[CH3:29][N:5]1[C@@H:6]2[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18][C@H:7]2[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]([C:14]([F:16])([F:17])[F:15])[C:13]=2[C:4]1=[O:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69054510HCID 69054510, compound

Product 1

HCID 69056920HCID 69056920, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH (9 mg of 60% in mineral oil, hexane-washed, 0.22 mmol) in 2 mL of THF at ambient temperature was added (3aS,9bR)-tert-butyl 5-oxo-6-(trifluoromethyl)-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]isoquinoline-2(9bH)-carboxylate from Example 13, Part A (52 mg, 0.145 mmol) as a solution in 2 mL of THF. The reaction was stirred for 20 min, at which time gas evolution had ceased and the reaction mixture was homogeneous. Then there was added iodomethane (0.023 mL, 0.36 mmol) and the reaction was allowed to stir at ambient temperature for 18 h. The reaction was quenched with water, diluted with EtOAc and washed with 1N HCl, sat'd aq NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (230-400 mesh silica gel, elution with 3:1 hexane/EtOAc) to afford 40 mg (74%) of the title compound. LRMS (ESI): 371.12 (M+H)+.

Workup

  1. stirringto stir at ambient temperature for 18 h
  2. customThe reaction was quenched with water
  3. additiondiluted with EtOAc
  4. washwashed with 1N HCl
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (230-400 mesh silica gel, elution with 3:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-f08132dddd2c4c5e96d4720661eca653
Source dataset
uspto-grants-2009_08
Patent number
US07572805B2

Reaction notes

Loading…